SLC1A3

Chr 5AD

solute carrier family 1 member 3

Also known as: EA6, EAAT1, GLAST, GLAST1

NCBI Gene: 6507ENSG00000079215UniProt: P43003

This gene encodes a member of a member of a high affinity glutamate transporter family. This gene functions in the termination of excitatory neurotransmission in central nervous system. Mutations are associated with episodic ataxia, Type 6. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2014]

Primary Disease Associations & Inheritance

Episodic ataxia, type 6MIM #612656
AD
UniProtEpisodic ataxia 6
364
ClinVar variants
25
Pathogenic / LP
0.99
pLI score· haploinsufficient
2
Active trials
Clinical Summary— SLC1A3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 187 VUS of 364 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.989
Z-score 4.00
OE 0.09 (0.04–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.79Z-score
OE missense 0.71 (0.64–0.80)
220 obs / 308.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.04–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.64–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 2 / 22.4Missense obs/exp: 220 / 308.3Syn Z: 0.21

ClinVar Variant Classifications

364 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic3
VUS187
Likely Benign71
Benign54
Conflicting17
22
Pathogenic
3
Likely Pathogenic
187
VUS
71
Likely Benign
54
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
20
0
22
Likely Pathogenic
0
0
3
0
3
VUS
6
144
30
7
187
Likely Benign
0
7
24
40
71
Benign
0
2
42
10
54
Conflicting
—17
Total615511957354

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC1A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Episodic ataxia, type 6

MIM #612656

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning.
Xu M et al.·Front Immunol
2023
The episodic ataxias.
Graves TD et al.·Handb Clin Neurol
2024Review
YTHDF1 regulates GID8-mediated glutamine metabolism to promote colorectal cancer progression in m6A-dependent manner.
Han Y et al.·Cancer Lett
2024
Episodic ataxias.
Jen JC et al.·Handb Clin Neurol
2018Review
Alleviated T cell exhaustion and SLC1A3-mediated stroma-remodelling dictate chemoimmunotherapy efficacy in oesophageal squamous cell carcinoma.
Xiang S et al.·Gut
2026Functional
[Hereditary episodic ataxia].
Riant F et al.·Rev Neurol (Paris)
2011Review
SLC1A3 contributes to L-asparaginase resistance in solid tumors.
Sun J et al.·EMBO J
2019
Episodic Ataxias: Faux or Real?
Giunti P et al.·Int J Mol Sci
2020Review
Genotype-phenotype relations for episodic ataxia genes: MDSGene systematic review.
Olszewska DA et al.·Eur J Neurol
2023Review
Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects.
Bianchin MM et al.·Curr Pain Headache Rep
2010Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Post Traumatic Stress DisorderComplex Posttraumatic Stress DisorderStress

Building Resilience at Schools: Emotional and Biological Assessment and Treatment of Traumatic Stress

RECRUITING
NCT05701111Phase NAStanford UniversityStarted 2024-02-23
Start with the Heart StudentsStart with the Heart TeachersCue Centered Therapy Counselors
Multiple SclerosisSpasticity

miR-142-3p as Potential Biomarker of Synaptopathy in MS

RECRUITING
NCT03999788Phase NANeuromed IRCCSStarted 2019-12-10
lumbar puncture and blood withdrawalIntermittent theta burst stimulation (iTBS) therapeutic protocol for spasticity

External Resources

Links to major genomics databases and tools